title: Axon degeneration is key component of neuronal death in amyloid-β toxicity.
abstract: Depending upon the stimulus, neuronal cell death can either be triggered from the cell body (soma) or the axon. We investigated the origin of the degeneration signal in amyloid β (Aβ) induced neuronal cell death in cultured in vitro hippocampal neurons. We discovered that Aβ1-42 toxicity-induced axon degeneration precedes cell death in hippocampal neurons. Overexpression of Bcl-xl inhibited both axonal and cell body degeneration in the Aβ-42 treated neurons. Nicotinamide mononucleotide adenylyltransferase 1 (Nmnat1) blocks axon degeneration in a variety of paradigms, but it cannot block neuronal cell body death. Therefore, if the neuronal death signals in Aβ1-42 toxicity originate from degenerating axons, we should be able to block neuronal death by inhibiting axon degeneration. To explore this possibility we over-expressed Nmnat1 in hippocampal neurons. We found that inhibition of axon degeneration in Aβ1-42 treated neurons prevented neuronal cell death. Thus, we conclude that axon degeneration is the key component of Aβ1-42 induced neuronal degeneration, and therapies targeting axonal protection can be important in finding a treatment for Alzheimer's disease.
authors.affiliation: Biology Department, University of Central Arkansas, Conway, AR 72035, United States.
authors.forename: Wilson M
authors.initials: WM
authors.lastname: Alobuia
authors.forename: Wei
authors.initials: W
authors.lastname: Xia
authors.forename: Bhupinder P S
authors.initials: BP
authors.lastname: Vohra
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D001369:Axons / Q000473:pathology*; D016923:Cell Death; D002478:Cells, Cultured; D006624:Hippocampus / Q000473:pathology*; D051379:Mice; D010446:Peptide Fragments / Q000633:toxicity*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)
keywords: Alzheimer’s; Amyloid-β; Axon degeneration; Bcl-xl; Nmnat